# A novel mechanism of virulence control in Porphyromonas gingivalis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $692,868

## Abstract

Abstract
Porphyromonas gingivalis is a major pathogen of severe adult periodontitis, a polymicrobial disease caused by
the coordinated action of a complex microbial community that leads to inflammation of tissues supporting the
teeth. A central hurdle limiting progress in periodontal disease research is the paucity of information detailing
microbial signals that correlate with clinical progression at a site from health to disease. Filling this void, we
recently reported metatranscriptome findings of the microbial community from human clinical samples during
periodontal disease progression and discovered that CRISPR (Clustered Regularly Interspaced Short
Palindromic Repeats)-associated proteins in the periodontopathogen P. gingivalis were highly up-regulated only
at those sites that progressed. CRISPRs-Cas systems are used by bacteria to prevent foreign DNA
incorporation, as occurs with a viral attack. The goal of this research program is to understand the role that
CRISPR-Cas systems have on virulence determinants of important periodontopathogens during disease
progression. A comprehensive analysis of the mutants will provide information required to increase our
understanding of not only CRISPR gene function, but also the contribution of these novel genes to virulence. To
this end we propose the following Specific Aims:
Aim 1. Identify targeted endogenous genes comparing transcriptome profiles of the wild-type and the mutants
growing intracellularly.
Aim 2. Determine the impact of CRISPR-associated genes on the innate immune host responses to P.
gingivalis.
Aim 3. Aim 3. Determine the role of CRISPR-Cas genes in the pathogenicity of P. gingivalis.
 We expect that this knowledge will facilitate the development of targeted approaches to prevent and treat
periodontitis by inhibiting specific Cas proteins essential for virulence. Such results will fundamentally advance our
understanding that such systems have in the metabolism of periodontal pathogens besides their traditional role
assigned as a mechanism of protection against foreign DNA. We believe that the team we have assembled for this
project has all the qualifications to accomplish successfully the goals proposed in the present application.

## Key facts

- **NIH application ID:** 10296292
- **Project number:** 1R01DE029775-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jorge Frias-Lopez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $692,868
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296292

## Citation

> US National Institutes of Health, RePORTER application 10296292, A novel mechanism of virulence control in Porphyromonas gingivalis (1R01DE029775-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10296292. Licensed CC0.

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